From the Guidelines
Cyclobenzaprine works as a centrally acting 5-HT2 receptor antagonist, acting as a skeletal muscle relaxant by affecting the brainstem and spinal cord levels, leading to decreased muscle tension and spasm. Its mechanism of action is complex, involving the reduction of tonic somatic motor activity at both the brain stem and spinal cord levels 1.
Key Mechanisms
- Centrally acting 5-HT2 receptor antagonist
- Skeletal muscle relaxant properties
- Structurally related to amitriptyline, with potential to interact with sedatives and anesthetic agents
- Peripheral and central anticholinergic activity, causing norepinephrine potentiation 1
Clinical Implications
- Used for short-term management of acute, painful musculoskeletal conditions associated with muscle spasm
- May cause adverse anticholinergic effects, including hallucinations, confusion, drowsiness, constipation, urinary retention, and dry mouth 1
- Concomitant use with monoamine oxidase inhibitors may increase the potential for serotonin syndrome
- Tapering over 2 to 3 weeks can help prevent withdrawal symptoms, such as malaise, nausea, and headache, after long-term use 1
From the FDA Drug Label
Cyclobenzaprine HCl relieves skeletal muscle spasm of local origin without interfering with muscle function. It is ineffective in muscle spasm due to central nervous system disease. Cyclobenzaprine reduced or abolished skeletal muscle hyperactivity in several animal models Animal studies indicate that cyclobenzaprine does not act at the neuromuscular junction or directly on skeletal muscle. Such studies show that cyclobenzaprine acts primarily within the central nervous system at brain stem as opposed to spinal cord levels, although its action on the latter may contribute to its overall skeletal muscle relaxant activity Evidence suggests that the net effect of cyclobenzaprine is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems
The mechanism of action of cyclobenzaprine is through its effects on the central nervous system, specifically at the brain stem level, which leads to a reduction of tonic somatic motor activity. This results in the relief of skeletal muscle spasm of local origin without interfering with muscle function. The key points of its mechanism of action are:
- Acts primarily within the central nervous system
- Does not act at the neuromuscular junction or directly on skeletal muscle
- Influences both gamma (γ) and alpha (α) motor systems
- Reduces tonic somatic motor activity 2
From the Research
Mechanism of Action of Cyclobenzaprine
- Cyclobenzaprine is a muscle relaxant that works by inhibiting tonic somatic motor function, likely through modulation of noradrenergic and serotonergic systems 3, 4.
- The exact mechanism of action of cyclobenzaprine remains elusive, but it is known to mediate its effects centrally 5, 4.
- Cyclobenzaprine has been shown to exhibit low nanomolar affinity for the cloned human histamine H1 receptor (H1R), as well as that expressed in both rat and mouse brain, and binds to the H1R in a noncompetitive manner 5.
- The muscle relaxant effect of cyclobenzaprine is thought to result from an activation of locus coeruleus neurons, leading to an increased release of noradrenaline in the ventral horn of the cord and the subsequent inhibitory action of noradrenaline on alpha motoneurones 6.
- Cyclobenzaprine's sedative effects are likely due to its off-target central antagonism of H1R, which modulates the high degree of sedation that patients experience 5.
Key Findings
- Studies have shown that cyclobenzaprine is effective in improving muscle spasm, reducing local pain and tenderness, and increasing range of motion in acute, painful musculoskeletal conditions 3, 7.
- Cyclobenzaprine has a reasonable safety profile, and overdoses are not as problematic as those for accepted tricyclic psychotherapeutic agents 4.
- The most common adverse effects of cyclobenzaprine are somnolence, dry mouth, fatigue, dizziness, sedation, and nausea 3, 7.